| 1) The terms BOS and CLAD should not be considered interchangeable or synonymous. Both are clinical terms that describe clinical syndromes. CLAD needs a precise definition, which has not yet been determined. |
| 2) The term BOS should be retained to denote allograft dysfunction with delayed onset and persistent decline in FEV1 (which is usually accompanied by evidence of airflow obstruction) that is not caused by other causes (some of which may be potentially reversible) of post-transplant loss of function. |
| 3) The timing of BOS onset and its subsequent course provide prognostic information and may be linked to different pathophysiological mechanisms. |
| 4) The identification and detailed definition of BOS phenotypes that correlate with prognosis and response to therapy may be useful in understanding the natural course of BOS and the development of more targeted treatment modalities. |
| 5) The following potential risk factors are associated with BOS: |
| a) Primary graft dysfunction (PGD) |
| b) AR including Minimal Grade A1 and higher AR grades |
| c) Lymphocytic bronchiolitis (LB) or Grade B rejection |
| d) Antibody-mediated rejection (AMR) |
| e) Gastro-oesophageal reflux (GOR) (acid and non-acid) |
| f) Cytomegalovirus (CMV) pneumonitis |
| g) Symptomatic community-acquired respiratory virus (CARV) infection |
| h) Colonisation and infection of the lung by Pseudomonas aeruginosa |
| i) Aspergillus colonisation or fungal pneumonitis |
| j) Autoimmune sensitisation to collagen V |
| k) Increased BAL neutrophils on BAL differential cell count |
| 6) BOS is generally suspected at an early stage when the FEV1 is ≤90% of baseline (i.e. BOS Grade 0-p) and/or the FEF25–75% is ≤75% of baseline in both bilateral and single lung transplant recipients. |
| 7) In most transplant centres, lung transplant recipients (including asymptomatic patients) receive sustained follow-up including routine clinical evaluation, spirometry (both in the clinic and in remote in-home settings), and other methods for monitoring allograft status (such as fibre-optic bronchoscopy, as appropriate). Such monitoring is generally sustained beyond the first 6–12 months following transplantation. |
| 8) When lung transplant recipients who have been clinically stable develop a decline in lung function, prompt clinical evaluation is usually performed to identify the likely cause. |
| 9) Routine postero-anterior and lateral chest radiographs are neither sensitive nor specific for diagnosing BOS. |
| 10) The findings of air trapping with expiratory views and/or mosaic attenuation patterns on HRCT imaging of the thorax support the presence of BOS, but lack sensitivity and specificity. |
| 11) Thoracic imaging assists in making a diagnosis of BOS by ruling out other causes of allograft function decline. |
| 12) Surveillance bronchoscopy can safely evaluate the lung allograft for occult abnormalities, although a beneficial effect on recipient survival and prevention of BOS has not been clearly demonstrated. In most transplant centres, surveillance bronchoscopy is routinely offered to lung recipients to potentially allow early detection of occult chronic lung allograft dysfunction and/or the presence of occult infection. |
| 13) Although bronchoscopy has poor sensitivity for the diagnosis of OB, bronchoscopy is frequently used to evaluate the lung allograft when evidence of clinical dysfunction is identified. |
| 14) The presence of BAL neutrophilia suggests that OB may be occurring in the lung allograft and that the allograft is at increased risk for progression to BOS; infection is a confounder and may be the cause of BAL neutrophilia, although infection and OB/BOS may coexist in the allograft. |
| 15) The presence of donor-specific antibody (DSA) suggests AMR when detected in the context of a delayed allograft functional decline. |
| 16) For lung transplant recipients who develop BOS and have evidence of allograft infection, aggressive measures to control and eradicate infection are routine. |
| 17) Within the various classes of commonly used immunosuppressive agents in lung transplant recipients, there is no definitive evidence of superiority of one drug or drug combination for prevention of BOS. |
| 18) Single-centre studies suggest that some less commonly used immunosuppressive agents (i.e. sirolimus, alemtuzumab and anti-thymocyte globulin) may improve outcomes in patients with BOS. |
| 19) Extracorporeal photopheresis (ECPP) and total lymphoid irradiation (TLI) are therapies that some institutions consider for selected patients with progressive BOS. |
BOS: bronchiolitis obliterans syndrome; CLAD: chronic lung allograft dysfunction; FEV1: forced expiratory volume in 1 s; AR: acute cellular rejection; BAL: bronchoalveolar lavage; FEF25–75%: forced expiratory flow at 25–75% of forced vital capacity; HRCT: high-resolution computed tomography; OB: obliterative bronchiolitis.